A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms

Area of Science:

• Neuroimmunology
• Dietary interventions
• Demyelinating diseases

Background:

• Dietary interventions have historically shown limited efficacy in treating multiple sclerosis (MS).
• Existing treatments for MS often focus on managing autoimmune responses or symptoms.
• There is a need for novel therapeutic strategies that can promote remyelination.

Purpose of the Study:

• To investigate the efficacy of a fasting-mimicking diet (FMD) in ameliorating symptoms and demyelination in a murine model of experimental autoimmune encephalomyelitis (EAE).
• To explore the underlying mechanisms of FMD's effects, including immune cell modulation and remyelination.
• To assess the safety, feasibility, and potential effectiveness of FMD and ketogenic diets in patients with relapsing-remitting multiple sclerosis (RRMS).

Main Methods:

• Utilized a murine experimental autoimmune encephalomyelitis (EAE) model to simulate MS.
• Administered periodic 3-day cycles of a fasting-mimicking diet (FMD).
• Assessed clinical severity, immune cell populations (Treg, TH1, TH17, APCs), corticosterone levels, and performed histological analysis for remyelination in EAE and cuprizone models. Preliminary human data from NCT01538355 was also analyzed.

Main Results:

• FMD significantly reduced clinical severity in EAE mice, with complete symptom reversal in 20% of animals.
• Improvements were linked to increased corticosterone and regulatory T (Treg) cells, and decreased pro-inflammatory cytokines, TH1/TH17 cells, and antigen-presenting cells (APCs).
• FMD promoted oligodendrocyte precursor cell regeneration and remyelination in both EAE and cuprizone models. Preliminary human data suggests FMD and ketogenic diets are safe and feasible for RRMS patients.

Conclusions:

• Periodic fasting-mimicking diets demonstrate therapeutic potential for multiple sclerosis by suppressing autoimmunity and promoting remyelination.
• The FMD's mechanism involves modulation of the immune system and enhancement of endogenous repair processes.
• Early clinical findings suggest FMD and ketogenic diets are viable options for managing relapsing-remitting multiple sclerosis, warranting further investigation.